1. Field of the Invention
The present invention relates to relates to a glycol chitosan derivative, which can form nano-sized self-assembled structures and has both temperature sensitivity and biodegradability so as to be suitable for use as a drug delivery system, as well as a preparation method thereof and a drug delivery system comprising the same.
2. Description of the Prior Art
Chitosan is a cationic polysaccharide derived from a chitin which is extracted from the shells of crustaceans such as crabs or shrimps. Generally, chitosan is obtained by removing about 50% or more of acetyl groups of C2 acetamide from chitin and has an N-acetylation degree of less than 50%. It is composed of β(1,4)-linked N-acetyl-D-glucosamine and D-glucosamine units.
Recently, chitosan has received attention as a functional biopolymer which can be used in diverse applications, such as foods, agricultural products, medicines, drugs and cosmetics, because it has various physical and chemical characteristics and physiological characteristics, such as biocompatibility, low toxicity and mucoadhesive properties.
However, chitosan having the above-described characteristics and advantages is insoluble in water, because adjacent molecules of chitosan are linked by a strong hydrogen bond. For this reason, in order to increase the utility of chitosan in the medical and bioengineering fields, it is required to develop chitosan derivatives which can be dissolved in various physiological conditions.
Glycol chitosan is a water-soluble chitosan derivative that is water-soluble at neutral pH due to a hydrophilic ethylene glycol group introduced therein. Previous studies reported that glycol chitosan is non-cytotoxic and biocompatible and stimulates the growth of chondrocytes at low concentration (Carreno-Gomez. B, Duncan. R, Int. J. Pharm. 1997, 148, 231; [8] D. K. Knight, S. N. Shapka, B. G. Amsden, J. Biomed. Mater. Res. Part A. 2007, 83, 787).
The amine groups present along the backbone of glycol chitosan can be modified to improve the in vivo efficiency of glycol chitosan. Glycol chitosan derivatives have been proposed in which various functional groups or molecules are introduced into the backbone of glycol chitosan in order to improve the characteristics of glycol chitosan or to impart new characteristics to glycol chitosan. Kwon et al. improved the hydrophobicity of glycol chitosan by linking 5β cholanic acid or deoxycholic acid thereto by covalent conjugation (K. Kim, S. Kwon, J. H. Park, H. Chung, S. Y. Jeong, I. C. Kwon, I. S. Kim, Biomacromolecules. 2005, 6, 1154; S. Kwon, J. H. Park, H. Chung, I. C. Kwon, S. Y. Jeong, Langmuir. 2003, 19, 10188). In animal studies, the glycol chitosan derivative exhibited extended blood circulation time and showed high tumor specificity in delivering various anticancer agents, such as doxorubicin, paclitaxel, docetaxel, camptothecin and cisplatin.
Although various studies on glycol chitosan derivatives have been conducted as described above, there has not yet been a report of an N-acetylated derivative of glycol chitosan.